Lewis acid-catalysed nucleophilic opening of a bicyclic hemiaminal followed by ring contraction: Access to functionalized L-idonojirimycin derivatives

• Published in: Carbohydrate research Vol. 472; pp. 65 - 71
• Main Authors: Auberger, N., Onfroy, B., Fontelle, N., Foucart, Q., Blériot, Y.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.01.2019; Elsevier
• Subjects: Bicycle opening; Biochemistry & Molecular Biology; Bridged Bicyclo Compounds, Heterocyclic / chemistry; Catalysis; Chemical Sciences; Chemistry; Chemistry, Applied; Chemistry, Organic; Hemiaminal; Imino Sugars / chemistry; Iminosugar; Lewis Acids / chemistry; Life Sciences & Biomedicine; Medicinal Chemistry; Molecular Structure; Organic chemistry; Physical Sciences; Piperidines / chemistry; Science & Technology; Skeletal rearrangement; Stereoisomerism; Hemiaminal; Iminosugar; Skeletal rearrangement; Bicycle opening; IMINOSUGAR C-GLYCOSIDES; POTENT; UDP-GALF MIMICS; BUILDING-BLOCKS; STEREOSELECTIVE-SYNTHESIS; INHIBITORS; SUGARS; CONCISE SYNTHESIS
• ISSN: 0008-6215; 1873-426X; 0008-6215
• DOI: 10.1016/j.carres.2018.11.008

The Lewis acid-catalyzed nucleophilic opening of a D-gluco-configured bicyclic hemiaminal has been examined. Several Lewis acids and silylated nucleophiles have been screened allowing the introduction of acetophenone, phosphonate or nitrile at the pseudoanomeric position in satisfactory yields and high 1,2 trans stereoselectivities. Their skeletal rearrangement triggered by the N-benzyl anchimeric assistance provided the corresponding L-ido-configured piperidines displaying various functional groups at C-6 position in good yield. [Display omitted] •Lewis acid-catalyzed nucleophilic opening of a D-gluco-configured bicyclic hemiaminal.•Ring contraction of the resulting azepane functionalized at C-1.•Access to L-idonojirimycin derivatives with orthogonal functions at C-1 and C-6.